The hydrolysis of chemical bonds within molecules is of critical importance in most metabolic (e.g., catabolic and anabolic) pathways in cells. A large family of enzymes which catalyze the cleavage of a bond with the addition of water, termed hydrolases, has been identified. Members of the hydrolase family are found in nearly all organisms, from microbes to plants to humans. Different classes of hydrolases are specific for an array of biological and chemical substrates. Members of the hydrolase family of enzymes include enzymes that hydrolyze ester bonds (e.g., phosphatases, sulfatases, exonucleases, and endonucleases), glycosidases, enzymes that act on ether bonds, peptidases (e.g., exopeptidases and endopeptidases), as well as enzymes that hydrolyze carbon-nitrogen bonds, acid anhydrides, carbon-carbon bonds, halide bonds, phosphorous-nitrogen bonds, sulfur-nitrogen bonds, carbon-phosphorous bonds, and sulfur-sulfur bonds (E. C. Webb ed., Enzyme Nomenclature, pp. 306–450, © 1992 Academic Press, Inc. San Diego, Calif.).
Hydrolases play important roles in the synthesis and breakdown of nearly all major metabolic intermediates, including polypeptides, nucleic acids, and lipids. As such, their activity contributes to the ability of the cell to grow and differentiate, to proliferate, to adhere and move, and to interact and communicate with other cells. Hydrolases also are important in the conversion of pro-proteins and pro-hormones to their active forms, the inactivation of peptides, the biotransformation of compounds (e.g., a toxin or a carcinogen), antigen presentation, and the regulation of synaptic transmission.
Ubiquitin carboxyl terminal hydrolases are responsible for de-ubiquitination in the cell and are critical in ubiquitin biosynthesis and proteosomal degradation. Because these proteins modulate ubiquitination, they are thought to be involved in numerous cellular processes which are mediated by ubiquitin including cell-cycle control, oncoprotein degradation, receptor function, regulation of transcription, stress responses, signaling pathways, antigen presentation, and the degradation of abnormal proteins (Johnston et al. (1999) EMBO J. 18:3877–3887).